This invention relates to macrolide compounds and their use, e.g., as antibacterial and antiprotozoal agents in animals, including humans. The invention also relates to methods of preparing compounds, intermediates useful in preparing compounds, and pharmaceutical compositions containing compounds. The present invention further includes methods of treating and/or preventing disease, e.g., bacterial and/or protozoal infections (or for other indications, e.g., cancer, inflammation, atherosclerosis, or gastric motility reduction), by administering compounds or compositions to subjects in need of such treatment.
Erythromycin and clarithromycin are well known macrolides. Other erythromycin-based macrolide compounds have been prepared, e.g., by introducing modifications at various positions of erythromycin or clarithromycin, e.g., as in: U.S. Pat. Nos. 4,331,803; 4,474,768; 4,517,359; 5,523,399; 5,527,780; 5,635,485; 5,804,565; 6,020,521; 6,025,350; 6,075,133; 6,162,794; 6,191,118; 6,248,719; 6,291,656; 6,437,151; 6,472,371; 6,555,524; US 2002/0052328; US 2002/0061856; US 2002/0061857; US 2002/0077302; US 2002/0151507; US 2002/0156027; US 2003/0100518; US 2003/0100742; US 2003/0199458; US 2004/0077557; WO 99/11651; WO 99/21866; WO 99/21869; WO 99/35157; EP 1 114 826; and J. Med. Chem., 46, 2706 (2003). Additional relevant publications are cited hereinbelow. These and all documents cited herein are fully incorporated by reference herein for all purposes, including for the teachings, modifications, and method(s) of modifying the subject positions on macrolide rings in various combinations. Thus, derivatives can include, e.g., modifications at the C-2, C-3, C-6, C-9, C-10, C-11, C-12, and C-13 erythromycin positions, etc., and corresponding azalide derivatives.
There is a desire for new macrolides in response to the increasing emergence of resistant organisms, to improve safety, and to improve activity spectrum, among other reasons.